Duchenne Muscular Dystrophy (DMD) is one of a group of muscular dystrophies characterized by the enlargement of muscles. DMD is one of the most prevalent types of muscular dystrophy and is characterized by rapid progression of muscle degeneration which occurs early in life. DMD is X-linked and affect mainly males—an estimated 1 in 3,500 boys worldwide.
The gene for DMD, found on the X chromosome, encodes a large protein—dystrophin. Dystrophin is required inside muscle cells for structural support: it is thought to strengthen muscle cells by anchoring elements of the internal cytoskeleton to the surface membrane and external structures. Without it, the muscle cannot produce force effectively and is susceptible to damage during contraction, eventually leading to muscle death and replacement by fatty and fibrous tissue. The accompanying immune response can add to the damage.
A mouse model for DMD exists, and is proving useful for furthering our understanding on both the normal function of dystrophin and the pathology of the disease. In particular, initial experiments that enhance the production of utrophin, a dystrophin relative, in order to compensate for the loss of dystrophin in the mouse are promising, and may lead to the development of effective therapies for this devastating disease. Accordingly, a need exists for enhancing utrophin production in order to treat muscular dystrophies and other myopathies.
MicroRNAs (miRNAs) are small, RNA molecules encoded in the genomes of plants and animals. These highly conserved, ˜21-mer RNAs regulate the expression of genes by binding to the 3′ or 5′-untranslated regions (3′-UTR or 5′-UTR) of specific mRNAs.
Although the first published description of an miRNA appeared ten years ago, only in the last two to three years has the breadth and diversity of this class of small, regulatory RNAs been appreciated. A great deal of effort has gone into understanding how, when, and where miRNAs are produced and function in cells, tissues, and organisms. Each miRNA is thought to regulate multiple genes, and since hundreds of miRNA genes are predicted to be present in higher eukaryotes the potential regulatory circuitry afforded by miRNA is enormous.
MicroRNAs may act as key regulators of processes as diverse as early development, cell proliferation and cell death, apoptosis and fat metabolism, and cell differentiation. Recent studies of microRNA expression implicate microRNAs in brain development chronic lymphocytic leukemia, colonic adenocarcinoma, Burkett's Lymphoma, and viral infection suggesting possible links between miRNAs and viral disease, neurodevelopment, and cancer. miRNAs are differentially expressed in myopathies and have been implicated in heart disease. Accordingly, a need exists for determining the role of microRNAs in utrophin production in order to treat myopathies or utrophin mediated diseases.